The present technology relates to routes for catalytic conversion of lysine or α-amino-ε-caprolactam to high value compounds that can be derivatized to prepare polymers, pharmaceuticals, and other useful materials.
Lysine is useful as a starting material for production of various azacyclic hydrocarbons. For example, lysine can be used to prepare α-amino-ε-caprolactam (“ACL”), which can then be deaminated to form epsilon-caprolactam, as described, e.g., in WO2005/123669 to Frost. Lysine can also be used to prepare pipecolinic acid (“PCA”), as described in B. Pal et al., Photocatalytic redox-combined synthesis of L-pipecolinic acid from L-lysine by suspended titania particles: effect of noble metal loading on the selectivity and optical purity of the product, J. Catal. 217:152-59 (2003) (available on-line at http://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/14649/1/JC2003-217-1.pdf).
Epsilon-caprolactam (hereinafter “caprolactam”) is a high-value compound that is in widespread used for nylon-6 production and is also useful, e.g.: for preparation of other polyamides for synthetic fibers, films, and coatings; for preparation of pharmaceutical compounds such as CNS depressants, muscle relaxants, anti-hypertensives, and angiotensin converting enzyme inhibitors; and as a plasticizer or cross-linking agent for various polymers. See, e.g., U.S. Pat. No. 6,504,047 to Knaup; U.S. Pat. No. 4,520,021 to Harris et al.; and J. H. Skerritt et al., Differential modulation of gamma-aminobutyric acid receptors by caprolactam derivatives with central nervous system depressant or convulsant activity, Brain Res. 331(2):225-33 (8 Apr. 1985).
PCA is also useful to form various PCA derivatives that are high value pharmaceuticals, examples of which include viral protease inhibitors, anti-convulsants, analgesics, and biliary disorder treatments. See, e.g., US 2001/0056184 to Noda et al.; U.S. Pat. No. 5,807,870 to Anderson et al.; U.S. Pat. No. 5,639,744 to Marchi et al.; U.S. Pat. No. 4,826,819 Vecchietti et al.; J. Heitman et al., Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast, Science 253:905-909 (23 Aug. 1991) [doi: 10.1126/science.1715094]; S. B. Shuker et al., Discovering high-affinity ligands for proteins: SAR by NMR, Science 274:1531-34 (29 Nov. 1996) [doi: 10.1126/science.274.5292.1531]; F. Couty, Asymmetric syntheses of pipecolic acid and derivatives, Amino Acids 16(3-4):297-320 (September 1999) (doi: 10.1007/BF01388174); and R. Paruszewski et al. Amino acid derivatives with anticonvulsant activity, Chem. Pharm. Bull. 49:629-31 (2001) (doi: 10.1248/cpb.49.629).
Additionally, because of their bioactive effects, caprolactam and PCA are also commonly used to prepare pharmaceutical candidate compounds, such as receptor and/or enzyme ligands. In some cases, the core of such a compound can comprise the caprolactam or PCA residue; in some cases a pendant moiety of the compound can comprise the caprolactam or PCA residue.
Employing readily obtainable, inexpensive lysine as a starting material offers the option of avoiding costly petrochemical synthesis of caprolactam. In regard to PCA, employing a lysine starting material provides the option of avoiding extensive purification steps for isolating commercial quantities of PCA from biological sources or for isolating large quantities of biological picolinic acid for reduction to PCA. Yet, to date there have been provided only a limited number of catalytic routes for converting lysine to such useful high-value materials. In particular, deamination of ACL has been described, but no routes utilizing hydrodenitrogenation has been identified.
Hydrodenitrogenation of petroleum has traditionally employed sulfided Co—Mo on Al2O3 and sulfided Ni—Mo on Al2O3. See, T. C. Ho, Catal. Rev. Sci. Eng. 1988:117-160; and I. Mochida et al., Japan Pet. Inst. 47:145-163 (2004). The amines in petroleum include heterocyclic amines, anilines, and aliphatic amines. Hydrodenitrogenations of substituted cyclohexylamines, other alkylamines, and substituted pyridine using sulfided Ni—Mo on Al2O3 have been mechanistically studied. See respectively: F. Rota et al., J. Catalysis 200:389-399 (2001) and F. Rota et al., J. Catalysis 202:195-199 (2001) (cyclohexylamines); Y. Zhao et al., J. Catalysis 222:532-544 (2004) and Y. Zhao et al., J. Catalysis 221:441-454 (2004) (other alkylamines); and M. Egorova et al., J. Catalysis 206:263-271 (2002) (substituted pyridine).
Gas phase hydrodenitrogenation of aliphatic amines, heterocyclic amines, and anilines have been reported using stoichiometric amounts of Pt on SiO2. See M. J. Guttieri et al., J. Org. Chem. 49:2875-2880 (1984). Pyridine hydrodenitrogenation has been studied using C-supported sulfided NiMo, Zr, Ag, Nb, Mo, Rh, and Pd catalysts. See M. J. Ledoux et al., J. Catalysis 115:580-590 (1989). Simultaneous hydrodenitrogenation of pyridine and hydrodesulfurization of thiophene employed C-supported Rh, Ru, Pd, Ir, and Pt. See, e.g., Z. Vit et al., J. Catalysis 119:1-7 (1989). In addition, quinoline hydrodenitrogenation has been examined using sulfided, C-supported W, Re, Os, Ir, Pt, Mo, Ru, Rh, Pd, V, Cr, Mn, Fe, Co, and Ni. See S. Eijsbouts et al., J. Catalysis 109:217-220 (1988).
However, hydrodenitrogenation of L-lysine and alpha-aminocaprolactam have not been previously reported. Therefore, it would be advantageous to provide alternative and improved methods for converting inexpensive lysine starting materials to useful, high value products such as caprolactam, PCA, and their derivatives, by novel hydrodenitrogenation routes that can be practiced in a convenient one-pot reaction format.